Search PubMed⌕ Search

Biomedical subjects

W Strober

Publications and source records attributed to W Strober.

At least 253 records · Page 14Linked to original sources
PubMed1975

In vitro studies of ulcerative ileojejunitis.

A patient with ulcerative ileojejunitis was studied by determination of HL-A phenotype, by measurement of jejunal IgA synthesis using a labeled amino acid incorporation technique, and by in vitro organ culture. The patient carried the HL-A8 phenotype in common with 87.5% of patients with gluten-sensitive enteropathy. During a period of exposure to dietary gluten, jejunal tissue from the patient exhibited in high IgA synthetic rate. In organ culture of the jejunal biopsy specimen there was an increase in alkaline phosphatase activity in the absence, but not in the presence, of gluten peptides. The synthetic rate value and the organ culture behavior are similar to those observed in patients with gluten-sensitive enteropathy in exacerbation. During a period in which the patient was not exposed to dietary gluten, including prolonged period of intravenous alimentation, jejunal IgA synthesis and organ culture behavior were studied repeatedly. In contrast to patients with gluten-sensitive enteropathy in remission (i.e., on a gluten-free diet), jejunal IgA synthesis did not decline. However, in organ culture in the patients tissue now behaved like that of other patients with gluten-sensitive enteropathy in remission: alkaline phosphatase activity increased during culture in the presence and absence of gluten peptides. These studies support the concept that ulcerative ileojejunitis is a complication of gluten-sensitive enteropathy in which escape from control by gluten restriction has occurred. They suggest that ulcerative ileojejunitis due to a supervening pathological process which is, at least in part, immunological in nature.

Adult↗
PubMed1975

Immunodeficiency in the Wiskott-Aldrich syndrome.

The immune system in the Wiskott-Aldrich syndrome is characterized by a host of paradoxes. Elements of the effector limbs of both humoral and cellular immunity such as immunoglobulin synthesis and in vitro lymphocyte proliferative, secretory and killer responses to nonspecific mitogens are intact. Yet, these patients fail to produce specific antibody normally following immunization and they are anergic. This combination of findings is consistent with a defect in the appropriate initiation of specific immune responses, ie a defect in the afferent limb of immunity.

Agglutinins↗
PubMed1974

Gluten-sensitive enteropathy: synthesis of antigliadin antibody in vitro.

The intestinal mucosa of patients with gluten-sensitive enteropathy responds to gluten challenge in vivo with a striking increase in IgA and IgM synthesis. Whether this increase in immunoglobulin synthesis is due in some part to the production of antigliadin antibodies is examined. Using an affinity chromatography technique it has been demonstrated that in six of seven patients with gluten-sensitive enteropathy approximately half of the net increase in IgA and IgM synthesis occurring after gluten challenge can be attributed to the synthesis of antigliadin antibody. These data strengthen the hypothesis that immunological phenomena are related to the pathogenesis of glutensensitive enteropathy.

Adolescent↗
PubMed1974

An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture.

Jejunal biopsy specimens from patients with gluten-sensitive enteropathy (GSE) (obtained during gluten challenge) as well as from normal individuals and patients with other gastrointestinal abnormalities were cultured in vitro for 48 h in the presence or absence of a peptic-tryptic digest (P-T digest) of gliadin. In the absence of gliadin the alkaline phosphatase activity in the biopsy specimens obtained from normal control individuals increased from an initial value of 384 +/- 83 U to a 48 h value of 561 +/- 151 U (mean +/- SD) (difference significant at P < 0.01). The initial alkaline phosphatase activity of specimens obtained from patients with GSE was strikingly lower than that of normals, 117 +/- 79 U, and increased to a 48 h value of 399 +/- 203 U (difference significant at P < 0.01). The biochemical change in cultured biopsy specimens of GSE patients correlated with increases in the length and regularity of brush borders of epithelial cells as seen with the electron microscope. In the presence of a P-T digest of gliadin, the alkaline phosphatase activity of biopsy specimens of control individuals increased from an initial value of 384 +/- 83 U to a 48 h value of 578 +/- 156 U. In contrast, the alkaline phosphatase activity of biopsy specimens of patients with GSE in exacerbation showed a markedly diminished increase in activity during 48 h of culture; in this case the initial activity was 117 +/- 79 U and the final activity was 203 +/- 93 U. This inhibitory effect on increase of alkaline phosphatase activity during organ culture was specific in that a P-T digest of casein (a protein not toxic in vivo to patients with GSE) had no effect on alkaline phosphatase increases in culture. Finally, these results obtained with biopsy specimens taken from patients with GSE in exacerbation were compared with results obtained from patients with GSE in remission. Alkaline phosphatase activity of specimens obtained from the latter group of patients also increased during culture but in this instance P-T digest of gliadin in the culture medium had no significant inhibitory effect. In conclusion, the inhibitory effect of gliadin on intestinal epithelial cells in organ culture represents an in vitro model of gluten-sensitive enteropathy. Inasmuch as this effect of gliadin is not seen in cultures of specimens taken from patients in remission, it appears that gliadin is not directly toxic to GSE jejunal mucosa per se, but rather toxicity requires the participation of an endogenous effector mechanism which must first be stimulated in vivo.

Adolescent↗
PubMed1974

Dermatitis herpetiformis. Immunologic concomitants of small intestinal disease and relationship to histocompatibility antigen HL-A8.

In the present study the relation between the gluten-sensitive intestinal lesion observed in dermatitis herpetiformis (DH) and in gluten-sensitive enteropathy (coeliac sprue) (GSE) was analyzed. Jejunal IgA synthesis in DH was estimated from the extent of incorporation of [(14)C]leucine into IgA in jejunal biopsy specimens during short-term in vitro culture. Patients with DH have significantly elevated incorporation values as compared to normal control individuals (18,880+/-13,614 vs. 5,830+/-3,190 cpm/mg tissue protein/ 90 min) (P < 0.02) and the degree of elevation correlates well with the degree of morphologic abnormality. Thus patients with DH are similar to patients with GSE where elevated local mucosal IgA synthesis has also been observed. By using both morphologic and immunologic criteria for evaluating intestinal status, patients with DH and intestinal disease were distinguished from patients with DH free of intestinal disease. Of the eight patients in the former group, seven carried HL-A8 (87.5%), an incidence which is strikingly similar to that observed in patients with GSE alone (88.5%). In contrast, of the seven patients in the latter group (without gastro-intestinal disease) two had HL-A8, an incidence (27%) not significantly different from that in the normal population (20%) (P > 0.1).Thus, both in respect to local mucosal increase in IgA synthetic rates and in respect to the association with HL-A8, the intestinal lesion of DH is similar to that of GSE.

Adult↗
PubMed1972

Impaired lymphocyte transformation in intestinal lymphangiectasia: evidence for at least two functionally distinct lymphocyte populations in man.

Intestinal lymphangiectasia is a disease characterized by hypoproteinemia and edema resulting from protein-losing gastroenteropathy secondary to abnormal intestinal lymphatics. Immunologic abnormalities associated with this disease include hypogammaglobulinemia, lymphocytopenia, skin anergy, and impaired allograft rejection. In the present study, the in vitro blastogenic transformation of lymphocytes from 12 patients with intestinal lymphangiectasia was assessed in order to gain insight into the mechanism of the cellular immune defect in this disease. Peripheral blood lymphocytes from patients with intestinal lymphagiectasia showed impaired in vitro transformation to nonspecific mitogens, specific antigens, and allogeneic cells when compared to equal numbers of cells from normal individuals. Patients with the most deficient in vitro reactivity tended to have the lowest serum albumin concentration and the lowest absolute lymphocyte count. Lymphocytes obtained from chylous effusions in each of the four patients studied transformed more vigorously than peripheral blood cells from the same patients. These results may be explained by the loss of recirculating, long-lived lymphocytes into the gastrointestinal tract, resulting in a relative depletion of the population of lymphocytes necessary for in vitro blast transformation. This disease thus represents a clinical analogue of animals with experimental thoracic duct drainage, and provides evidence for the existence, in man, of two functionally distinct lymphocyte populations. In addition, these findings establish a new mechanism of impaired delayed hypersensitivity and defective in vitro lymphocyte transformation, i.e. the gastrointestinal loss and consequent depletion of the long-lived, recirculating population of lymphocytes from the peripheral lymphocyte pool.

Adolescent↗
PubMed1972

The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia.

The metabolism of low density lipoprotein (LDL, beta lipoprotein) was studied in 10 normal individuals and 10 patients with familial type II hyperlipoproteinemia using purified radioiodinated LDL. Over 97% of the label was bound to the protein moiety of LDL and therefore the turnover data reflect the fate and distribution of LDL-apoprotein. Comparison of the metabolic behavior of biologically screened and unscreened labeled LDL preparations in dogs as well as the analysis of the urinary excretion of radioiodide derived from labeled LDL degradation in humans indicated that no significant denaturation resulted from the isolation, purification, and labeling techniques. The plasma concentration of LDL-cholesterol in normals was 105+/-21 mg/100 ml (mean +/-1 SD) in contrast to 254+/-47 mg/100 mg in patients with type II hyperlipoproteinemia; these values corresponded to LDL-apoprotein concentrations of 63+/-13 mg/100 ml and 153+/-30 mg/100 ml, respectively. Despite these differences in concentration, the synthetic rate of LDL-apoprotein in both groups was not significantly different (14.43+/-1.75 mg/kg per day in normals vs. 15.01+/-1.71 mg/kg per day in type II) nor was there any difference in the fraction of the total exchangeable LDL which was in the intravascular space (68.4+/-4.3% vs. 73.3+/-5.2%). However, the fractional catabolic rate of LDL in normal individuals differed significantly from that of patients with type II hyperlipoproteinemia (0.462+/-0.077/day in normals vs. 0.237+/-0.044/day in type II) and correspondingly the biological half-life of LDL was significantly prolonged (3.08+/-0.35 days normals vs. 4.68+/-0.44 days in type II). These data indicate that the pathologic elevation of plasma LDL concentration in the individuals with type II hyperlipoproteinemia studied here is due to a decreased fractional rate of LDL degradation rather than to an abnormality of LDL synthesis. This defect of catabolism may be the primary defect in type II hyperlipoproteinemia or, alternatively, may be secondary to an underlying abnormality in lipid metabolism.

Adult↗
PubMed1972

Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy.

HL-A phenotypes were determined in 24 unrelated patients with gluten-sensitive enteropathy (GSE) using a lymphocyte microcytotoxicity test. 21 of the 24 patients had HL-A8 in the second segregant series, a frequency of 0.875. In contrast, the HL-A8 frequency in 200 normal individuals was 0.215 (difference significant at P < 0.002), and in 6 patients with villous atrophy due to tropical sprue or hypogammaglobulinemia the HL-A8 frequency was 0.17 (difference from normal not significant). The HL-A types in the families of three HL-A8 positive patients with GSE indicated that the HL-A8 antigen was inherited as an autosomal dominant. Frequencies of the other HL-A antigens in the GSE group did not differ significantly from that of the normal group. These findings are compatible with the hypothesis that GSE is due to the presence of an abnormal "immune response (Ir) gene," leading to the production of pathogenic antigluten antibody or, alternatively, to the presence of a particular membrane configuration leading to the binding of gluten to epithelial cells with subsequent tissue damage.

Agammaglobulinemia↗
PubMed1972

The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia.

The present study was directed toward determining the role of the kidney in the metabolism of various classes of serum proteins and to define the urinary protein excretion patterns and the pathogenesis of disorders of protein metabolism in patients with proteinuria. To this end, the metabolic fates of a small protein, lambda-L chain (mol wt 44,000), and a protein of intermediate size, IgG (mol wt 160,000), were studied in controls and patients with renal disease. Controls metabolized 0.28%/hr of circulating IgG and 22.3%/hr of circulating lambda-L chain. All the IgG and 99% of the lambda-L chain was catabolized with the remaining lambda-L chain lost intact into the urine. The kidney was shown to be the major site of catabolism for small serum proteins. Three distinct disorders of protein metabolism were noted in patients with renal tubular disease and tubular proteinuria, glomerular disease (the nephrotic syndrome), and disease involving the entire nephrons (uremia), respectively. Patients with renal tubular disease had a 50-fold increase in the daily urinary excretion of 15-40,000 molecular weight proteins such as lysozyme and lambda-L chains. Serum IgG and lambda-L chain survivals were normal; however, the fraction of the over-all lambda-L chain metabolism accounted for by proteinuria was increased 40-fold whereas endogenous catabolism was correspondingly decreased. Thus, tubular proteinuria results from a failure of proximal tubular uptake and catabolism of small proteins that are normally filtered through the glomerulus. Patients with the nephrotic syndrome had a slight increase in lambda-L chain survival whereas IgG survival was decreased and the fraction of IgG lost in the urine was markedly increased. Here, abnormal glomerular permeability to proteins of intermediate size is the basic abnormality. Patients with uremia had a normal IgG survival but a four to 10-fold prolongation of lambda-L chain survival due to loss of entire nephrons, the major site of metabolism of these proteins. This results in an increase (up to 10-fold) in the serum concentration of lambda-L chain, lysozyme, and other small biologically active proteins, a phenomenon that may be of importance in causing some of the manifestations of the uremic syndrome.

Adult↗